Abstract
Alzheimer’s disease (AD) is the most common fatal neurodegenerative disease of the elderly worldwide. The identification of AD biomarkers will allow for earlier diagnosis and thus earlier intervention. The aim of this study was to find such biomarkers. It was observed that the expression of Alix was significantly decreased in brain tissues and serum samples from AD patients compared to the controls. A significant correlation between Alix levels and cognitive decline was observed (r = 0.80; p < 0.001) as well as a significant negative correlation between Alix and Aβ40 in serum levels (r =−0.60, p < 0.001). The receiver operating characteristic curve (ROC) analysis showed the area under the curve (AUC) of Alix was 0.80, and the optimal cut-off point of 199.5 pg/ml was selected with the highest sum of sensitivity and specificity. The diagnostic accuracy for serum Alix was 74%, with 76% sensitivity and 71% specificity respectively, which could differentiate AD from controls. In addition, the expression of Alix was found to be significantly decreased in AD compared to vascular dementia (VaD). ROC analysis between AD and VaD showed that the AUC was 0.777, which could be indicative of the role of serum Alix as a biomarker in the differential diagnosis between AD and VaD. Most surprisingly, the decreased expression of Alix was attenuated after the treatment of Memantine in different AD animal models. In conclusion, our results indicate the possibility of serum Alix as a novel and non-invasive biomarker for AD for the first time.
Highlights
Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases in the elderly, accounting for 60–80% of all cases (Sabayan and Sorond, 2017; Garre-Olmo, 2018)
Alix was reported to have a role to play in cholesterol homeostasis by facilitating the interaction between the E3-ubiquitin ligase NEDD4–1 and its targets, ATP-Binding Cassette (ABC) transporters, including ABCG1 and ABCG4 (Alrosan et al, 2019)
It was reported that ABCG1 could reduce the synthesis of amyloid β (Aβ) peptides by enhancing cholesterol efflux from neurons to apolipoprotein E, and might play an additional proposed role in restricting the brain entry of Aβ in AD (Sano et al, 2016; Dodacki et al, 2017)
Summary
Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases in the elderly, accounting for 60–80% of all cases (Sabayan and Sorond, 2017; Garre-Olmo, 2018). Many recent pieces of research have revealed a great deal about AD (Hodson, 2018; Jack et al, 2018), the exact pathogenesis is not yet fully known. Current treatments can only help improve the clinical symptoms, but cannot delay or reverse the progression of AD. The identification of AD biomarkers would have great values to aid in the diagnosis of AD. To date, there is no non-invasive and cost-effective biomarker to improve the diagnosis
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